Beschreibung:
Abstract Background: Gene expression profiling in breast cancer offers the potential to improve prognostic accuracy, treatment choice, and health outcomes in women diagnosed with early-stage breast cancer. Numerous gene-profiling assays are now available, which can be applied to a single tumor specimen to provide physicians with a more complete basis for treatment decisions. MammaPrint is a DNA microarray-based in vitro diagnostic that measures the activity of 70 genes to estimate whether patients are at high risk or low risk of developing metastases within the first 10 years after curative surgery. BluePrint is an 80-gene molecular subtyping profile that discriminates between three breast cancer subtypes: Luminal, HER2, and Basal. TargetPrint provides a quantitative measurement of estrogen receptor (ER), progesterone receptor (PR), and HER2, and can serve as a reliable second pathology assessment for locally-assessed parameters. Oncotype DX measures expression of five reference genes and 16 cancer-related genes, quantifying the risk of distant recurrence in patients with ER+ early breast cancer who are treated with adjuvant hormonal therapy, and predicting clinical benefit with additional adjuvant chemotherapy. Trial design: PROMIS is a prospective, observational, case-only study that will investigate the additional value of MammaPrint, BluePrint and TargetPrint in women with an intermediate Oncotype DX score. An initial CRF – capturing baseline patient characteristics, pathology information, Oncotype DX score and the recommended treatment plan – will be completed before receiving the MammaPrint result. A second CRF – capturing the recommended treatment – will be completed within 4 weeks after receiving the MammaPrint result. Eligibility: The study will include women aged ≥18 years with histologically proven invasive stage I-II, node-negative, hormone receptor-positive, HER2-negative breast cancer and Oncotype DX score of 18–30 who signed informed consent. Objectives: The objectives of the study are to: 1. Describe the frequency of chemotherapy + endocrine versus endocrine-alone decisions in Oncotype DX intermediate score patients.2. Assess the impact of MammaPrint on chemotherapy + endocrine versus endocrine-alone treatment decisions.3. Assess the distribution of MammaPrint Low and High Risk in patients with an intermediate recurrence score.4. Assess concordance of TargetPrint ER, PR and HER2 results with Oncotype DX ER, PR and HER2 and with locally assessed IHC/FISH ER, PR and HER2.5. Compare clinical subtype based on IHC/FISH ER, PR, HER2 and Ki-67 (if available) with BluePrint molecular subtype. Statistical methods: As the project is exploratory, sample size calculations do not apply as only descriptive statistics will be used. The frequency of chemotherapy + endocrine versus endocrine-alone decisions in Oncotype DX intermediate score patients will be calculated before and after receiving the MammaPrint result. A Chi-square test will be performed for the comparison of the two proportions. Accrual: A total of ∼300 eligible patients will be enrolled from multiple institutions. Clinical trial registry number: NCT01617954 Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT3-4-01.